Rhodopsin Trafficking and Mistrafficking

Nemet, Ina; Ropelewski, Philip; Imanishi, Yoshikazu

doi:10.1016/bs.pmbts.2015.02.007

Cited by 69 publications

(49 citation statements)

References 174 publications

(227 reference statements)

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“…Rhodopsin is the light receptor in rod photoreceptor cells and is the predominant protein species in ROS discs. The light receptor is synthesized in the rod inner segment and transported to the base of the ROS, where it is incorporated into the membrane of newly synthesized ROS discs [8-12]. Rhodopsin initiates the first steps of vision via phototransduction by absorbing incoming photons and, upon photoactivation, binding and activating the heterotrimeric G protein transducin [13].…”

Section: Introductionmentioning

confidence: 99%

Adaptations in rod outer segment disc membranes in response to environmental lighting conditions

Rakshit

Senapati

Parmar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The light-sensing rod photoreceptor cell exhibits several adaptations in response to the lighting environment. While adaptations to short-term changes in lighting conditions have been examined in depth, adaptations to long-term changes in lighting conditions are less understood. Atomic force microscopy was used to characterize the structure of rod outer segment disc membranes, the site of photon absorption by the pigment rhodopsin, to better understand how photoreceptor cells respond to long-term lighting changes. Structural properties of the disc membrane changed in response to housing mice in constant dark or light conditions and these adaptive changes required output from the phototransduction cascade initiated by rhodopsin. Among these were changes in the packing density of rhodopsin in the membrane, which was independent of rhodopsin synthesis and specifically affected scotopic visual function as assessed by electroretinography. Studies here support the concept of photostasis, which maintains optimal photoreceptor cell function with implications in retinal degenerations.

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Section: Introductionmentioning

confidence: 99%

Adaptations in rod outer segment disc membranes in response to environmental lighting conditions

Rakshit

Senapati

Parmar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Many ciliary proteins contain short sequences used for their specific targeting [8, 9]. One of the better studied cases is the visual pigment rhodopsin, which contains a four amino acid (V[S/A]PA) targeting sequence at its C-terminus known as the VXPX motif [10, 11]. Human patients containing mutations in either the V or P residues exhibit autosomal dominant retinitis pigmentosa [12], and deletion of these residues in mice results in rhodopsin mislocalization followed by photoreceptor cell death [13–15].…”

Section: Introductionmentioning

confidence: 99%

Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration

et al. 2017

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Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4’s role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period. Arf4 deletion in photoreceptors did not cause protein mislocalization or retinal degeneration, as expected if Arf4 played a role in protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney did not cause cystic disease, as expected if Arf4 were involved in general ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal period resulted in growth restriction, severe pancreatic degeneration and early death. These findings are consistent with Arf4 playing a critical role in endomembrane trafficking, particularly in the pancreas, but not in ciliary function.

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“…We did not observe an 254 effect on Crb ( Figure 5D) or basolateral Nrv ( Figure 5E), suggesting that traffic to the stalk and 255 the basolateral membrane was not affected. opposing orientations (for review see Nemet et al, 2015). In vertebrate PRCs, rhodopsin is made 279 in the inner segment (IS) and transported to the vertebrate equivalent of the rhabdomere, the outer 280 segment (OS).…”

Section: Microtubule Motor Protein Dynein Is Required For Rh1 and Eysmentioning

confidence: 99%

“…whereas kinesin is important in trafficking from the base of the OS to its tip (Nemet et al, 2015). 285…”

Section: Microtubule Motor Protein Dynein Is Required For Rh1 and Eysmentioning

confidence: 99%

Identification of genes required for apical protein trafficking in Drosophila photoreceptor cells

Laffafian

Tepaß

2019

Preprint

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Drosophila photoreceptor cells (PRCs) are highly polarized epithelial cells. Their apical membrane is further subdivided into the stalk membrane and the light-sensing rhabdomere. The photo-pigment Rhodopsin1 (Rh1) localizes to the rhabdomere, whereas the apical determinant Crumbs (Crb) is enriched at the stalk membrane. The proteoglycan Eyes shut (Eys) is secreted through the apical membrane into an inter-rhabdomeral space. Rh1, Crb, and Eys are essential for PRC development, normal vision, and PRC survival. Human orthologs of all three proteins have been linked to retinal degenerative diseases. Here, we describe an RNAi-based screen examining the importance of approximately 240 trafficking-related genes in apical trafficking of Eys, Rh1, and Crb. We found 28 genes that have an effect on the localization and/or levels of these apical proteins and analyzed several factors in more detail. We show that the Arf GEF protein Sec71 is required for biosynthetic traffic of both apical and basolateral proteins, that the exocyst complex and the microtubule-based motor proteins dynein and kinesin promote the secretion of Eys and Rh1, and that Syntaxin 7/Avalanche controls the endocytosis of Rh1, Eys, and Crb.Article summeryPhotoreceptor cells (PRCs) rely on polarized vesicle trafficking to deliver key secreted and transmembrane proteins to their correct locations. Failure to do so causes defects in PRC development, function, and survival leading to retinal disease. Using the fruit fly Drosophila as a model we have identified 28 genes that are required for the trafficking of the three apical proteins Rhodopsin 1, Crumbs, and Eyes Shut. Human homologs of all three genes are associated with retinal degeneration. We characterized several genes to reveal novel mechanisms of vesicle trafficking in photoreceptor cells at different points in the biosynthetic or endocytotic pathways.

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Rhodopsin Trafficking and Mistrafficking

Cited by 69 publications

References 174 publications

Adaptations in rod outer segment disc membranes in response to environmental lighting conditions

Adaptations in rod outer segment disc membranes in response to environmental lighting conditions

Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration

Identification of genes required for apical protein trafficking in Drosophila photoreceptor cells

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